Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Activation of endogenous retroviruses during brain development causes an inflammatory response

Jönsson, Marie E LU ; Garza, Raquel LU orcid ; Sharma, Yogita LU ; Petri, Rebecca LU ; Södersten, Erik ; Johansson, Jenny G LU ; Johansson, Pia A LU ; Atacho, Diahann Am LU orcid ; Pircs, Karolina LU orcid and Madsen, Sofia LU , et al. (2021) In EMBO Journal 40(9). p.106423-106423
Abstract

Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to... (More)

Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
EMBO Journal
volume
40
issue
9
pages
106423 - 106423
publisher
Oxford University Press
external identifiers
  • scopus:85101832411
  • pmid:33644903
ISSN
1460-2075
DOI
10.15252/embj.2020106423
language
English
LU publication?
yes
id
01956095-bde8-48fb-8ad2-a7955c2d8692
date added to LUP
2021-05-05 09:30:51
date last changed
2022-08-11 21:55:48
@article{01956095-bde8-48fb-8ad2-a7955c2d8692,
  abstract     = {{<p>Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.</p>}},
  author       = {{Jönsson, Marie E and Garza, Raquel and Sharma, Yogita and Petri, Rebecca and Södersten, Erik and Johansson, Jenny G and Johansson, Pia A and Atacho, Diahann Am and Pircs, Karolina and Madsen, Sofia and Yudovich, David and Ramakrishnan, Ramprasad and Holmberg, Johan and Larsson, Jonas and Jern, Patric and Jakobsson, Johan}},
  issn         = {{1460-2075}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{106423--106423}},
  publisher    = {{Oxford University Press}},
  series       = {{EMBO Journal}},
  title        = {{Activation of endogenous retroviruses during brain development causes an inflammatory response}},
  url          = {{http://dx.doi.org/10.15252/embj.2020106423}},
  doi          = {{10.15252/embj.2020106423}},
  volume       = {{40}},
  year         = {{2021}},
}